Identification of Peptide Vaccine Candidates for Prostate Cancer Patients with HLA-A3 Supertype Alleles

e16037 Background: We have shown that the AE37 vaccine (Ii-Key modified HER2(776-790) peptide) is safe and induces HER2/neu–specific cellular immune responses in patients with prostate cancer (Perez SA et al Clin. Cancer Res. 2010, 16:3495). We now present data from 4-year immunological assessments of prostate cancer patients who received AE37. Methods: Seventeen patients in a phase I study were given 6 doses of AE37 at monthly intervals and one additional dose a year after initiating treatment. Immunological testing to assess active versus suppressive immunity was conducted one month (intermediate-term immunomonitoring [ITI]) and 3 years (long-term immunomonitoring [LTI]) after the final dose of AE37. ELISPOT and proliferation assays were conducted to assess cytokine secretion and mitogenic response to antigen. DTH reactions were measured to assess in vivo immune response to antigen. All assays were conducted using native HER2(776-790) peptide (AE36). The percent Treg cells and ng/ml TGFβ were determined as markers for immune suppression. Results: Neither ELISPOT nor proliferation assays were statistically different at LTI compared to ITI. While clearly above pre-vaccine responses, the drop in DTH was statistically significant (p < 0.05). Similarly, the increase in Treg cells and circulating TGFβ was also statistically significant. An increase of >200 % in PSA-doubling time at any point during the study was observed in 6/17 patients, with 3 retaining this effect to 5 years. Conclusions: AE37 generates immunological memory associated with possible clinical efficacy in spite of Tregs and TGF-β levels returning at 4 years after being decreased for up to 6 months after initial AE37 vaccination. These results support further randomized testing of the AE37 vaccine. Clinical trial information: 2006-003299-37. [Table: see text]

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Immunological efficacy of herbal medicines in prostate cancer patients treated by personalized peptide vaccine

Cancer Science ◽

10.1111/cas.13397 ◽

2017 ◽

Vol 108 (12) ◽

pp. 2326-2332 ◽

Cited By ~ 7

Author(s):

Noriko Koga ◽

Fukuko Moriya ◽

Kayoko Waki ◽

Akira Yamada ◽

Kyogo Itoh ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Peptide Vaccine ◽

Herbal Medicines ◽

Personalized Peptide Vaccine

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Haptoglobin promoter polymorphism rs5472 as a prognostic biomarker for peptide vaccine efficacy in castration-resistant prostate cancer patients

Cancer Immunology Immunotherapy ◽

10.1007/s00262-015-1756-7 ◽

2015 ◽

Vol 64 (12) ◽

pp. 1565-1573 ◽

Cited By ~ 2

Author(s):

Hiromitsu Araki ◽

Xiaoliang Pang ◽

Nobukazu Komatsu ◽

Mikiko Soejima ◽

Nawoe Miyata ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Vaccine Efficacy ◽

Prognostic Biomarker ◽

Peptide Vaccine ◽

Promoter Polymorphism ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant

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Effect of immunization with the ii-key modified HER2/neu(776-790) (AE37) peptide vaccine on pre-existent immunity to PSA in HLA-A24+ prostate cancer patients: Association with increased AE37-specific immunologic responses.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e15125 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e15125-e15125

Author(s):

Sonia A. Perez ◽

Eleftheria Anastasopoulou ◽

Efi Pappou ◽

Nikolaos Fragkiskos Pistamaltzian ◽

Eric von Hofe ◽

...

Keyword(s):

Prostate Cancer ◽

T Cells ◽

Phase I ◽

Cancer Patients ◽

Phase I Study ◽

Peptide Vaccine ◽

Therapeutic Vaccine ◽

Immunological Responses ◽

Her 2 ◽

Mhc Alleles

e15125 Background: In solid tumors such as prostate cancer, novel biomarkers are needed for assessing immunological responses and clinical efficacy. By using dextramers specific for PSA we have retrospectively analyzed CD8+ T cell frequencies in patients with HER-2/neu+ prostate cancer who had received the AE37 vaccine in a phase I study (Perez SA et al Clin. Cancer Res. 2010, 16:3495). AE37 binds to numerous MHC alleles (Perez SA et al Clin. Cancer Res. 2010, 16:3495) (Salazar LG, Clin Cancer Res. 2003, 9:5559) encouraging its use as a therapeutic vaccine for general HER-2/neu+ cancer patients. Methods: CD8+ Dextramer+ T cells were measured, retrospectively, in the blood (which was stored in N2 liquid) of HLA-A24+ (n= 12) and HLA-A2+ (n=12) patients. Blood lymphocytes collected before, during and 6-months post vaccination were all analyzed with the same method involving direct labeling with HLA A24/PSA(153-161)-FITC and PerCP-conjugated anti-CD8 monoclonal antibody. Results: 8 of 12 HLA-A24+ patients had preexistent immunity to PSA as evidenced by the increased percentages of CD8+ HLA-A24/PSA(153-161)+ T cells in pre-vaccination samples. All of these patients had shown increased in vitro (IFNγ-based ELISPOT assay) and in vivo (DTH) immunological responses to the AE37 vaccine in the phase I study (Perez SA et al Clin. Cancer Res. 2010, 16:3495). Importantly, this preexistent immunity was significantly boosted in 5 patients during vaccinations with AE37, was slightly increased in 2 others, whereas in one patient no changes were observed during vaccinations. Conclusions: These results suggest that HLA-A24 expression along with preexistent immunity to PSA(153-164) may represent biomarkers based on which HER-2/neu+ patients can be selected most likely to benefit from vaccination with AE37. A phase II trial is warranted for validating these results. Given the promiscuity of AE37, it would be intriguing to examine if preexistent immunity to other prostate antigens restricted by various MHC alleles exist and to demonstrate an increase in preexistent immunity in association with a positive immunologic response to vaccination with AE37.

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